The presence of a thymus is critical to human female reproductive development. Its congenital absence leads to total ovarian dysgenesis. In laboratory rats and mice, neonatal thymectomy results in ovarian failure. During this same neonatal period, injections of estradiol-17beta and testosterone also adversely affect female reproductive development. The traditional view has been that the two steroids damage the hypothalamus so that it never develops an estrogen-responsive positive feedback mechanism. In this theory, testosterone is effective only because it is aromatized to estradiol-17beta in the steroid-injected animal. Results from our studies cast some doubt on this theory in its entirety, and implicate the thymus/immune system as a causative mediator of the deleterious action of the two steroids. Our overall plan is to examine the role of components of the thymus/immune system in reproductive development. Specifically, our experiments are designed to ask the following: 1) Is the thymus a mediator of neonatal steroid-induced sterility? 2) Can the effects of neonatal steroid- injection be reversed by components of the immune system? 3) Can the effects of neonatal steroid-injection be transferred by thymic components to a thymectomized nonsteroid-injected animal? 4) Does neonatal steroid- injection induce steroid receptors in lymphocytes? 5) Can glucocorticoids prevent estrogen/androgen-induced anovulation? 6) Does neonatal steroid- injection affect ovarian in situ leukocyte distribution? Mice are widely used for research in cancer, genetics, reproductive physiology, pharmacology, toxicology, teratology, and immunology. Much of what is known about the immune system has resulted from using the mouse as a model. As a result, many of the cellular components within the murine immune system have been characterized. Most important from our point of view is the research that has already been done on the thymic maturation of mouse T-lymphocytes. The results from the proposed research should advance our understanding of the mechanism of thymus-related control of the reproductive system, especially during the sensitive neonatal period. In addition, it is anticipated that our studies will inevitably aid in the further understanding of such reproductive functions as the estrous/menstrual cycle; follicular growth vs. atresia; ovulation; and fertility vs. sterility.